Kits and Methods for Treating Post Traumatic Stress Disorder (PTSD) and Hot Flashes

ABSTRACT

The present invention is directed to kits and methods for the treatment of a patient suffering from post-traumatic stress disorder (PTSD) and/or hot flashes by an administration of a mixture produced by a combination of a long acting local anesthetic combined with clonidine. The combination of the two pharmaceuticals produces a significant increase in duration and speed of onset of sympathetic blockade, increased intensity of the sympathetic blockage as well as the reduction of local anesthetic absorption locally. The combination significantly improves the efficacy, speed of onset and block intensity of a right sided cervical sympathetic ganglion injection (RCSGI) leading to increased length of resolution of PTSD and hot flashes as well as reducing the potential for complications related to absorption of the local anesthetic.

This application claims priority to provisional patent application Ser.No. 61/889,895, filed Oct. 11, 2013, to the extent allowed by law.

FIELD OF THE INVENTION

The present invention is directed to methods and kits for the treatmentof post traumatic stress disorder (PTSD) and hot flashes byadministering a right sided cervical sympathetic ganglion injection(RCSGI) for delivery of a mixture of long acting anesthetic andinjectable clonidine to a patient in need of treatment for PTSD.

BACKGROUND OF THE INVENTION

Post-Traumatic Stress Disorder (PTSD) is a devastating and complexpathological anxiety condition that is characterized by severe distressand impairment in mental and physical functioning. Symptoms typicallyinclude intense anxiety, hyper-arousal, flashbacks and sleepdisturbances. The impact and consequences for individuals diagnosed withPTSD include depression, substance abuse, violence, inability tomaintain intimate relationships, inability to maintain parentalrelationships, suicide and premature mortality. PTSD is also a publichealth dilemma because nearly 80% of residents experience traumaticevents in their lifetime. Women are twice as likely to develop PTSDsymptoms than men due to the prevalence of sexual assaults.

Individuals impacted with PTSD require swift medical intervention.Current standard treatments for PTSD are pharmacotherapy andpsychotherapy. Pharmaceutical treatments include selective serotoninreuptake inhibitors [SSRIs]). Treatment of PTSD is considered successfulif there is a reduction in the severity, frequency and intensity ofsymptoms. Women tend to respond to psychotherapy and SSRI treatment,however may patients remain non-responsive or only partially responsiveto such treatments, and there is no consensus on the most beneficialmeans of treating such patients.

Approximately 10% of PTSD affected patients seek treatment within twelvemonths of the PTSD stimulating traumatic event. The decision to seektreatment includes factors such as cost-benefit analysis, hesitationwith psychotherapy and consideration of concerns of the side effects ofSSRIs and other pharmacological agents such as nausea, tremors,nervousness and other side effects.

The occurrence of PTSD in the US military has been captured in headlinesfor several years. There is a marked increase in the PTSD due to therecent military operations. The number of veterans committing suicidedaily has increased to 22 per day in the US, compared to the prior ratecited by the Department of Veterans Affairs at 18 per day. Possibly upto 30% of returned veterans suffer from PTSD and over 400,000 veteransreceive disability benefits due to PTSD.

The cost of treatment is also to be considered, not only for thepatient, but to the health care system and to communities. The costs inhealth care can range from $6,000 and $30,000 per year and the projectedcost of disability claims alone for veterans was estimated to be $650billion over the next 20 years. However, when a patient is not treated,this cost is immeasurable in potential loss of life through suicide andviolence. The overall efficacy of PTSD treatments in the military(excluding SGB) is 25% as per report in Hoge, C. W., Interventions forWar-Related Posttraumatic Stress Disorder: Meeting Vetrans Where TheyAre, JAMA 2011; 306:549-51.

Another health concern causing significant discomfort for many women isthe occurrence of hot flashes. Although the cause of hot flashes is notwell known, they occur when the blood vessels at the skin's surfacedilate to cool an individual. Hot flashes can be accompanied byperspiration, rapid heart rate or chills. The severity of symptoms canvary for women, particularly those going through menopause and severalfactors can trigger symptoms such as caffeine, alcohol, tight clothing,spicy food and stress.

Other than avoiding triggers and some lifestyle adjustments, such askeeping cool and incorporating exercise into the routine, sufferers ofhot flashes may be treated with pharmaceuticals such as birth controlpills, blood pressure medicines, antidepressants and other hormonetreatments. All of these treatments pose risks of side effects such asblood clots, cancers, headache, nausea, anxiety, drowsiness, tremors,diarrhea, constipation, sexual side effects and more. Due to thenegative side effects of current treatments, many women opt to not betreated and suffer the symptoms of hot flashes, even for many years.

As is noted above the current treatments of PTSD and hot flashes areineffective and the need for enhancing the reach of treatment,engagement by patients, adherence to treatment protocol, andacceptability of treatments cannot be over stated.

SUMMARY OF THE INVENTION

The methods and kits of the present invention are directed to methodsand kits for the treatment of post traumatic stress disorder (PTSD) orhot flashes by administering a right sided cervical sympathetic ganglioninjection (RCSGI) for delivery of a mixture of long acting anestheticand injectable clonidine to a patient in need of treatment for PTSD orhot flashes.

The kits of the present invention minimally contain the therapeuticallyactive ingredients of the present invention including a long actinganesthetic and clonidine. The long lasting anesthetic and clonidine maybe present in the kit in two separate vials unmixed in solution or as aprecipitate to be solubilized on-site prior to administration. The longlasting anesthetic and clonidine may also be present in one vial, mixedin solution or as a precipitate to be solubilized on-site prior toadministration. The kit may optionally comprise a package insert onpaper or on a data storage device. The kit may optionally comprise atleast one syringe. The kit may optionally comprise at least one bluetowel.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view showing various vertebrae and nerves in theneck and needle placement for right-sided cervical sympathetic ganglioninjection (RCSGI).

FIG. 2 demonstrates the connections from the stellate ganglion to theparts of the brain, the most relevant is the connection from Stellateganglion to amygdala, which is the part of the brain primarily active inPTSD. Stellate is also connected to hypothalamus that controlstemperature.

DETAILED DESCRIPTION

Stellate ganglion block (SGB) and right sided cervical sympatheticganglion injection (RCSGI) offers a new treatment option for PTSD or hotflashes. SGB is a commonly used anesthetic technique that hastraditionally been administered for pain relief. The injection of localanesthetic into these nerves blocks impulses, which may in turn reducepain, swelling, color, and sweating changes in the upper extremities andmay improve mobility. Stellate ganglion blocks are known as part of thetreatment of Reflex Sympathetic Dystrophy (RSD), Sympathetic MaintainedPain, Complex Regional Pain Syndrome (CRPS), and Herpes Zoster(shingles) involving the head and face and/or upper extremities.Classically, SGB is an injection of cervical sympathetic ganglion at C7and T1 levels. SGB can be administered on the left and/or right side ofthe neck, and the anesthetic volume used for SGB varies from 5 cc to 25cc.

Prior treat PTSD by utilization of a right-sided cervical sympatheticganglion injection (RCSGI) was called the Chicago Block (CB), morespecifically, a right sided cervical sympathetic ganglion block at C-6cervical level used for PTSD treatment, 7 cc of bupivacaine withfluoroscopic guidance. CB is different from SGB because CB is rightsided only, at C6 and not C7. The long acting anesthetic is not used tocontrol pain in the CB procedure. This use is called a “para anesthetic”application of a sympathetic block. For simplicity, the abbreviation,RCSGI, will be used in the description henceforth.

Bupivacaine and Ropivacaine have been used in the Chicago Blockprocedure. Most had positive results, the first placebo controlled trialwas performed by the Navy and demonstrated no difference between RCSGIand placebo. This study used Ropivacaine and ultrasound guidance, notxray guidance. The Stellate Ganglia block looked promising, but it wasconsidered to be nothing more than placebo effect by the study performedby the Navy. Preliminary data from the Navy was positive leading to thestudy.

The present invention details the efficacy of RCSGI for treatment ofPTSD based on the synaptic neurological connection from StellateGanglion (SG) to the part of the brain associated with PTSD, mainlyamygdala and hypothalamus, as illustrated diagrammatically in FIG. 2.Stellate Ganglion connections to intra-cerebral structures have beendemonstrated by the use of pseudorabies virus injections (Westerhaus andLoewy, 2001). This virus allows identification of neural pathwayconnections one to three synapses away from the injection site, hereStellate ganglion.

Further evidence of the sympathetic ganglion and the cerebrum connectionwas reported in a rat model. In this experiment specific cholinotoxinwas injected in the hippocampus (HP), leading to cholinergic denervationof the HP with eventual growth of peripheral sympathetic fibers into theHP, originating from the superior cervical ganglion (Harrell LE). Thus,we believe modulation of SG can modify amygdala activity and eventuallyPTSD symptoms by the pathways reported above.

The second set of reports focuses on nerve growth factor (NGF) increaseas a physiological response to stress. This has been reported in chronicstress by Dr. Smith (Smith, 1996) and acute stress by Dr. Alleva (Allevaet al., 1996). NGF is the best understood member of the neurotropicfamily, its function is to regulate a variety of signaling events suchas cell differentiation and survival and apoptosis (death) of neurons(Snider, 1994). The stress modulated NGF increase is thought to activatea cascade of events eventually leading to an increase in norepinephrine(NE) levels, and leading to an increase in PTSD symptoms, ashypothesized by Dr. Lipov in 2009 (Lipov), the details are summarizedbelow.

Intracerebral NGF increase has been shown to increase NGF concentrationin the SG due to retrograde transport of NGF from the intracerebral siteto the SG (Johnson et al., 1987). Next, NGF increase at the stellateganglion has been shown to lead to sprouting (new nerve growth) at thesympathetic end terminals, which are NGF dependent (Chen et al., 2001),which in turn, cause increased norepinephrine (NE) levels. This cascadehas been seen in a rat model, where infusion of NGF in the rat brainleads to an increase in NE (Isaacson and Billieu, 1996). Evidence pointsto NE being involved in PTSD where urine levels of NE are known toincrease in PTSD (Kosten et al., 1987). Thus, it appears that traumatriggers a neurobiological cascade that ultimately leads to PTSD.

We believe this cascade is reversed by the application of a localanesthetic to the stellate ganglion, with eventual reduction of NE. Thisview is supported by the fact that local anesthetics suppress nervegrowth factor-mediated neurite outgrowth (Takatori T), reversing theprocess. Further support of our theory is the report by Dr. Masatakafinding that serum NE is reduced following SGB in a non-PTSD setting(Masataka Y), and significant urinary reduction of NE in 2 patients withPTSD following SGB (Lipov). Thus, as a local anesthetic is applied tothe SG, PTSD symptoms may resolve. Presumably, the more NGF is reducedthe more neurite growth is removed followed by reversal of PTSD to agreater degree and resulting brain changes will occur. Finally, the moreintense and the longer the sympathetic block of the SG the more intenseis the effect of the sympathetic block on PTSD. The mixture of a localanesthetic and clonidine is the focus of this invention and is known toproduce a more intense and more prolonged sympathetic blockade.

The mixture is believed to have a more profound effect on suppression ofa nerve growth factor-mediated neurite outgrowth, producing more intensereduction or removal of neurite outgrowth, reducing NE levels in thebrain treating PTSD and hot flashes more effectively.

The following are injectates (substances injected) used for SGB andRCSGI:

Local Anesthetic:

Sympathetic ganglion blockade has been performed utilizing localanesthetics. Usually, long acting anesthetic has been used to have aprolonged sympathectomy (or sympathetic effect). Epinephrine may becombined with a local anesthetic to reduce local absorption of the localanesthetic and increase the length of the effect. This approach has atheoretical problem of epinephrine affecting sympathetic effect, sinceepinephrine is one of the agonists of the sympathetic nervous system.

Phenol:

Sympathetic ganglion blockade has been performed utilizing phenol, whichis a neurolytic or a more permanent way to block a ganglion, however itis associated with significant and common complications such aspersistent Horner's (droopy eye) and vocal cord nerve trauma as well asothers that may be permanent.

Local Anesthetic and Steroid Combination:

The unfortunate practice of combination of steroids and local anestheticcontinues without medical reason for it. This practice is associatedwith strokes and should not continue.

Local Anesthetic Mixed with Clonidine:

The duration and magnitude of vasodilating effect induced by sympatheticblock with the addition of different concentrations of clonidine tomepivacaine was studied. In dogs, mean arterial pressure (MAP), heartrate (HR), and right as well as left brachial artery blood flow (BABF)were measured before and after stellate ganglion block (SGB) used assympathetic block. The experimental protocol was designed as follows: 1)Group 1: left SGB using 0.5% mepivacaine 1 ml (n=6), 2) Group 2: leftSGB using the addition of clonidine 0.5 microgram to 0.5% mepivacaine 1ml (n=6), 3) Group 3: left SGB using the addition of clonidine 5micrograms to 0.5% mepivacaine 1 ml (n=6).

The results: MAP showed no significant change throughout the study ingroups 1 and 2. In group 3, MAP was lower than that of group 1. HRshowed no significant change throughout the study in the three groups.Left BABF increased significantly after left SGB in the three groups.The duration of increased BABF in group 2 was the longest, and that ingroup 3 was the shortest among them. Right BABF after left SGB decreasedsignificantly throughout the study in the three groups, and themagnitude of the decrease in BABF in group 3 was the highest among them.The study concluded that the sympathetic block with the addition ofclonidine to local anesthetics increases both duration and magnitude ofits vasodilating effect. However, sympathetic block with the addition ofhigher doses of clonidine to local anesthetics may induce shorterduration and lower magnitude of vasodilating effect compared with localanesthetics alone.

Although clonidine has been shown to prolong analgesia in centralneuraxial blocks, its use in peripheral nerve blocks remainscontroversial. A systematic review was performed of the currentliterature to determine the benefit of adding clonidine to peripheralnerve blocks.

A systematic, qualitative review of double-blind randomized controlledtrials on the benefit of clonidine as an adjunct to peripheral nerveblock was performed. Studies were identified by searching PubMed(www.ncbi.nlm.nih.gov/entrez) and EMBASE (www.embase.com) databases(July 1991 to October 2006) for terms related to clonidine as an adjunctto peripheral nerve blocks. Studies were classified as supportive if theuse of clonidine demonstrated reduced pain and total analgesicconsumption, or prolonged block duration versus negative if nodifference was found. Twenty-seven studies were identified that met theinclusion criteria. Five studies included a systemic control group. Thetotal number of patients reviewed was 1,385. The dose of clonidinevaried from 30 to 300 μg. Overall 15 studies supported the use ofclonidine as an adjunct to peripheral nerve blocks with 12 studiesfailing to show a benefit. Based on qualitative analysis, clonidineappeared to prolong analgesia when added to intermediate-acting localanesthetics for axillary and peribulbar blocks. Clonidine improvesduration of analgesia and anesthesia when used as an adjunct tointermediate-acting local anesthetics for some peripheral nerve blocks.Side-effects appear to be limited at doses up to 150 mug. Evidence islacking for the use of clonidine as an adjunct to local anesthetics forcontinuous catheter techniques. Further research is required to examinethe peripheral analgesic mechanism of clonidine.

In another study, a cervical sympathetic block (bupivicaine, clonidine)of a 12-15 ml solution of bupivicaine 0.5% containing 50 mcg ofclonidine for cervical sympathetic block was administered in a singleinjection. It is unclear from the literature if clonidine, mixture withlocal anesthetic has a clinical effect

The anesthetics of the present invention may be any short or long actinglocal anesthetic, or their amides or esters. Short acting anestheticsmay have anesthetic effect ranging from minutes to hours on a subjectbeing anesthetized. Long acting anesthetics may have anesthetic effectranting from minutes to months on a subject being anesthetized. Thelocal anesthetics may be short acting esters, such as chloroprocaine,procaine, novocaine; short acting amides such as lidocaine, prilocalneand mepivacaine; long acting esters, such as tetracaine and amethocaine;long acting amides, such as bupivicaine, levobupivacaine, ropivacaine,dibucaine and etidocine; or atypical anesthetics such as, benzocaine,cocaine, cyclomethycaine, cimethocaine, larocaine, piperocaine,propoxycaine, proparacaine, trimecaine or combinations thereof. Theclonidine is used as an alpha-2-adrenergic agonist, however other activeagents may also be used in the mixture with the anesthetic. Otheralpha-2-adrenergic agonists that may used in the mixture of the presentinvention are Guanfacine, Guanabenz, Guanoxabenz, Guanethidine,Xylazine, Tizanidine, Methyldopa, Fadolmidine or Dexmedetomidine andcombinations thereof.

Generally, to prepare the active pharmaceutical ingredients foradministration, at least one long lasting anesthetic is mixed withclonidine in a preservative free 0.9% saline solution. Upon mixing theactive pharmaceutical ingredients, the solution is pushed through a 22micron filter and brought to desired volume with preservative free 0.9sterile saline.

The present invention may be prepared using standard methods in the artfrom solubilizing and mixing the active pharmaceutical ingredients todelivery. However, by way of example the preparation may be formulatedin a Class 5 sterile environment or better using an aseptic technique. Adesired amount of clonidine and a long acting local anesthetic, such asbupivacaine, powders are weighed and dissolved in a minimal volume ofpreservative free sterile water. A sufficient amount of 0.9%preservative free (PF) sterile saline to reach 90% of the desiredvolume. The resultant solution may be pushed through a 0.22 micronfilter of appropriate size to accommodate the total volume beingprepared into a sterile syringe to be used to redistribute the finalvolume into the ultimate dispensing container(s). An additional volumeof the 0.9% preservative free saline solution may be pushed through thesame filter to establish 100% of the desired volume. New, virgin filtersmay be used to redistribute the pharmaceutical mixture into a newsyringe or the ultimate dispensing container(s). The mixture may betransferred into sterile vials or syringes, sealed and labeledappropriately.

The kit of the present invention may comprise one vial with the activepharmaceutical ingredients solubilized, mixed, filtered and brought tovolume in one vial. In another embodiment, the active pharmaceuticalingredients may be provided in separate vials either in solution, as aprecipitate or in a lyophilized form for reconstitution orsolubilization, filtering and bringing up to volume on-site ofadministration or other location.

The vials of the kit, housing the active pharmaceutical ingredients, maybe glass, clear glass, amber or any other vials used in the art. Theactive pharmaceutical ingredients may be housed in sterile syringes thatare ready for the surgical forum, or in any other housing known in theart.

The kit may optionally contain an empty or filled syringe known in theart, for use in the surgical forum. By way of examples, the syringes maybe 22 g quince needle 3½ inches, 10 cc syringe labeled DYE, 10 ccsyringe labeled mixture, 10 cc syringe labeled local, 2 18 gauge 1 inchneedles, 1 25 gauge 1½ inch needle and the like.

The kit may also contain a package insert in any form such as paper oron a data storage device which includes specifications of thepharmaceutical ingredients, preparation instructions, dosage variations,storage instructions, administration instructions, side effects of thepharmaceutical ingredients, contraindications for administration,stability data or any other information relevant to the use of thepresent invention for patient care or physician information. The kit mayalso contain blue towels or other devices to maintain sterility. InPTSD, psychological tools such as PCL M and non-military, as well assimilar tools, may be used. For hot flashes, psychological tools such asSloan scale or equivalent, as well as a screening tool for sleepdisorders may be used.

Storage instructions provided for the present invention, and foroptional inclusion in the kit of the present invention, are thefollowing: Storage at Room Temperature 15-30 C up to 24 hours;Refrigerated 2-8 C up to 3 days; or Frozen (−20 to −40 C) up to 45 days.The long acting anesthetics typically have a long shelf life sometimesup to two years and clonidine should be kept at room temperature andaway from direct sunlight and moisture. A clonidine and bupivicanemixture is typically stable at room temperature for at least 90 days.

In an embodiment of the invention, the long lasting anesthetic of thepresent invention is bupivacaine, a white crystalline powder that isfreely soluble in 95 percent ethanol, soluble in water, and slightlysoluble in chloroform or acetone.

In relation to dosing, the dose administered will be dependent on theneeds of each individual patient. However the long acting localanesthetic may range from 0.005 μg/cc to 40 μg/cc. In an embodiment, theanesthetic concentration may vary from 0.01% to 2% per cc. The dose ofthe clonidine may range from 0.5 μg/cc to 1000 μg/cc. In an embodiment,clonidine is 0.5 μg/cc. The volume of the dose administered to a patientmay range from 2-50 cc. The dose administered may be approximately 7 cc.If the patient weighs between 70-100 lb, then the dose may beapproximately 6 cc. If the patient weighs between 50-70 lb then the dosemay be approximately 5 cc. The number of administrations may vary, butthe minimum administration to see effective results to eliminate orminimize PTSD symptoms or hot flashes is one administration. Additionaladministrations may be administered with gaps in between administrationof anywhere from 1-50 days.

By way of example, and not limitation, the preparation of the presentinvention is administered as an injectable, right sided cervicalsympathetic ganglion block at C-6 cervical level. The administration mayalso be a left sided cervical sympathetic ganglion block at C-6 cervicallevel, as illustrated diagrammatically in FIG. 1. The administration ofthe present invention has been, and may be administered higher than C-6,for instance at C-3, on the right or left side. The administration ofthe present invention may also be lower than C-6, for instance at C-7,on the right or left side. The administration of the present inventionmay be at multiple cervical targets in the same instance ofadministration. The active pharmaceutical ingredients may beadministered via other routes of administration known in the art such asintracerebral, epidural, topical, enteral, parenteral, intramuscular,intradermal, intravenous, subcutaneous, intrathecal and the like.

In a case study, a patient having PTSD was administered bupivicane andclonidine in a RCSGI. The first three injections were without clonidine.The fourth was with clonidine. The clonidine block began working withinfive minutes of the procedure and with a much stronger effect.

A 43 year old female patient was treated CB, both without clonidine andwith clonidine, and reported a significantly more effective result withclonidine over the local anesthetic alone.

In a pediatric application, an 11 year old female was the first toreceive an injection intended to relieve PTSD related symptoms. Theprocedure involved a local anesthetic mixed with clonidine delivered bya shot in the patient's neck in a procedure that is similar to anepidural given to women in labor. The anesthetic mixture blocks asubstance that is called nerve growth factor which is believed toincrease in PTSD patients. That condition then leads to excessiverelease of a hormone that triggers the “fight or flight” response in thebrain. Blocking the nerve growth factor can then calm the PTSD patient,allowing the patient to get past basic survival reactions and betterdeal with life. The effect on the patient was immediate. This patientpreviously was terrified of car rides, however after this treatmentslept on the car ride home. Previously the patient reported that therewas no safe place in her mind, however after the treatment reported notworrying so much anymore. The objectives of the treatment were to allowthe patient to sleep better, to reduce the psychiatric medications shetakes and allow for her psychotherapy to be more effective. All of theseobjectives were accomplished after the administration of the treatmentof the present invention.

Yet another patient who is a survivor of a shooting responded to thetreatment described in the present invention. The shooting was at pointblank range and her PTSD manifested in fright and memories as though shewas being hunted down and shot again. She received the ganglion blockprocedure known as the Chicago Block, receiving an injection of a minuteamount of local anesthetic, which was a mixture of bupivicane andclonidine. The patient reported that she can now talk about thefrightening events of when she was shot.

In yet another patient, a 54 year old woman in menopause had significantimprovement of her hot flashes immediately following SGB treatment. Themixture of bupivicane and clonidine was used on this patient as well.

The treatment of the instant invention intervenes when a personexperiences significant anxiety and their nerve growth factor, or NGF,levels spike. That growth factor causes the stellate ganglion—a mass ofnerve cells on the right side of the neck—to promote increases in thebody's production of norepinephrine—a stress hormone—and kicks thebody's “fight or flight”. The anesthetic in the Chicago Block seems tohalt the body's overproduction of NGF. When the nerve growth slows andthe body stops overproducing stress hormones, a person's physicalresponse changes.

Although preferred embodiments of the disclosure are illustrated anddescribed in connection with particular features and formulations, thepresent invention can be adapted for use with a wide variety ofanesthetics and pharmaceutical actives. Other embodiments andequivalents are envisioned within the scope of the claims. Variousfeatures of the disclosure have been particularly shown and described inconnection with the illustrated embodiments. However, it must beunderstood that the particular embodiments merely illustrate the presentinvention, and that the invention is to be given its fullestinterpretation within the terms of the claims.

1. A method for treating a patient with a medical condition selectedfrom the group consisting of post-traumatic stress disorder and hotflashes, comprising: administering an injection of a local anestheticand clonidine, said injection is administered at a cervical sympatheticganglion.
 2. The method of claim 1, wherein said local anesthetic isselected from the group consisting of lidocaine, mepivacaine,bupivicaine, ropivacaine and combinations thereof.
 3. (canceled)
 4. Themethod of claim 1, wherein said local anesthetic is mixed with saidclonidine into a solution.
 5. The method of claim 1, wherein said localanesthetic is bupivacaine.
 6. (canceled)
 7. The method of claim 1,wherein said injection is administered as a right sided cervicalsympathetic ganglion injection.
 8. The method of claim 1, wherein saidinjection is administered as a left sided cervical sympathetic ganglioninjection.
 9. The method of claim 1, wherein said injection isadministered at cervical vertebrae
 6. 10. The method of claim 1, whereinsaid injection is administered at cervical vertebrae
 3. 11. The methodof claim 1, wherein said injection is administered at cervical vertebrae7.
 12. The method of claim 1, wherein said local anesthetic isadministered in a range from 0.005 μg/cc to 40 μg/cc.
 13. The method ofclaim 1, wherein said clonidine is administered in a range from 0.5 to1000 μg/cc.
 14. (canceled)
 15. (canceled)
 16. (canceled)
 17. A kitcontaining said local anesthetic and said clonidine of claim 1,comprising at least one vial.
 18. The kit of claim 17, additionallycomprising at least one syringe.
 19. The kit of claim 17, additionallycomprising at least one needle.
 20. The kit of claim 17, additionallycomprising a package insert.
 21. The kit of claim 17, additionallycomprising a manual for pre and post injection screening for PTSD andhot flashes diagnosis.
 22. (canceled)
 23. (canceled)
 24. (canceled) 25.(canceled)